Widening Phenotypic Spectrum of AADC Deficiency, a Disorder of Dopamine and Serotonin Synthesis

Helman, Guy; Pappa, M.; Pearl, Phillip L.

doi:10.1007/8904_2014_327

Cited by 30 publications

(20 citation statements)

References 17 publications

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“…Thus, if a child presents with oculogyric crises accompanied by unexplained movement and developmental delays, especially dystonia, AADCD should be considered. Four patients presented epileptic seizures with EEG findings, but only nine patients with epileptic seizures have been reported worldwide (Brun et al, ; Chang, Sharma, & Marsh, ; Helman, Pappa, & Pearl, ; Ito et al, ; Manegold et al, ). Although epileptic seizures are uncommon in AADCD, the differentiation of epileptic seizures from involuntary nonepileptic movements, is indispensable for the appropriate antiepileptic drugs treatment of patients.…”

Section: Discussionmentioning

confidence: 99%

Aromatic L‐amino acid decarboxylase deficiency in 17 Mainland China patients: Clinical phenotype, molecular spectrum, and therapy overview

Dai

2020

Molec Gen & Gen Med

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Background Aromatic L‐amino acid decarboxylase deficiency (AADCD) is a rare, autosomal recessive inherited disorder which is characterized by neurological and vegetative symptoms. To date, only 130 patients with AADCD have been reported worldwide. Methods We demonstrated 14 previously undescribed patients together with three reportedly patients in Mainland China. Full clinical information was collected, and disease‐causing variants in the DDC gene were detected. Results The common clinical manifestation of patients, including intermittent oculogyric crises, retarded movement development, and autonomic symptoms. Notably, a patient showed bone‐density loss which have not been reported and two mildly phenotype patients improved psychomotor function after being prescribed medication. The most common genotype of Mainland Chinese AADCD is the splice‐site variant (IVS6+4A> T; c.714+4A> T), which accounts for 58.8%, followed by c.1234C>T variant. Three novel compound heterozygous variants, c. 565G>T, c.170T>C, and c.1021+1G>A, were firstly reported. It is important to recognize the milder phenotypes of the disease as these patients might respond well to therapy. Besides, we discovered that patients may presented with milder if found to be compound heterozygote or homozygote for one of the following variants c.478C>G, c.853C>T, c.1123C>T, c.387G>A, and c.665T>C. Discussion The clinical data of the cohort of 17 patients in Mainland China broaden the clinical, molecular, and treatment spectrum of aromatic L‐amino acid decarboxylase deficiency.

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Section: Discussionmentioning

confidence: 99%

Aromatic L‐amino acid decarboxylase deficiency in 17 Mainland China patients: Clinical phenotype, molecular spectrum, and therapy overview

Dai

2020

Molec Gen & Gen Med

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“…However, patients display severe hypotonia and abnormal involuntary movements which dramatically interfere with motricity and communication abilities; therefore, their cognitive level is difficult to evaluate. Other milder phenotypes have been recently described (Helman et al 2014;Leuzzi et al 2015), suggesting the heterogeneity and phenotypic widening of the disease.…”

Section: Discussionmentioning

confidence: 91%

Chronic Diarrhea in l-Amino Acid Decarboxylase (AADC) Deficiency: A Prominent Clinical Finding Among a Series of Ten French Patients

Spitz¹,

Nguyen

Roche

et al. 2016

JIMD Reports

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“…aadc converts l-doPa to da and is considered the rate-limiting enzyme for the synthesis of biogenic amines. Studies have shown that aadc deficiency is a rare pediatric neuro-metabolic disease in children and indicate that defects in the aadc gene result in neurotransmitter deficiencies (52)(53)(54)(55)(56). COMT and mao are important da-degrading enzymes.…”

Section: Discussionmentioning

confidence: 99%

Effect on the dopaminergic metabolism induced by oral exposure to simazine during the prepubertal period in rats

et al. 2017

Int J Mol Med

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The herbicide simazine is widely used in agricultural and non-agricultural fields. Studies have shown that simazine inhibits the proliferation of dopaminergic cells and affects the developmental differentiation of dopamine neurons. However, little is known about the effects of simazine on dopaminergic metabolism. Therefore, the present study examined the effects of simazine on Sprague‑Dawley (SD) rats from weaning to puberty (40 days exposure). Simazine was administered orally to SD rats at doses of 0, 12.5, 50 and 200 mg/kg body weight. The contents of dopamine (DA), levodopa, dihydroxy-phenyl-acetic acid and homovanillic acid in the striatum were then examined by high-performance liquid chromatography with a fluorescence detector. Quantitative polymerase chain reaction and western blotting were used to analyze the mRNA and protein expression of aromatic amino acid decarboxylase (AADC), tyrosine hydroxylase, orphan nuclear hormone (Nurr1), dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT2), monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). The results indicated that simazine influenced the synthesis, transport and metabolism of DA and led to a reduction of DA levels in the striatum. One potential underlying mechanism is decreased levels of Nurr1, DAT and VMAT2 impacting upon the transport of DA; another is the decreased level of AADC and increased levels of MAO and COMT impacting upon the synthesis and metabolism of DA. These factors may eventually lead to neurological disorders of the dopaminergic system.

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Widening Phenotypic Spectrum of AADC Deficiency, a Disorder of Dopamine and Serotonin Synthesis

Cited by 30 publications

References 17 publications

Aromatic L‐amino acid decarboxylase deficiency in 17 Mainland China patients: Clinical phenotype, molecular spectrum, and therapy overview

Aromatic L‐amino acid decarboxylase deficiency in 17 Mainland China patients: Clinical phenotype, molecular spectrum, and therapy overview

Chronic Diarrhea in l-Amino Acid Decarboxylase (AADC) Deficiency: A Prominent Clinical Finding Among a Series of Ten French Patients

Effect on the dopaminergic metabolism induced by oral exposure to simazine during the prepubertal period in rats

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